Bovine papillomavirus type 1 E6-induced sensitization to apoptosis is distinct from its transforming activity

The bovine papillomavirus type 1 (BPV-1) E6 oncoprotein induces tumorigenic transformation of murine C127 cells and stimulates transcription when targeted to a promoter. We have previously shown that C127 cells expressing BPV-1 E6 exhibited increased tumor necrosis factor alpha (TNF)-mediated apoptosis. To understand the mechanisms by which BPV-1 E6 sensitizes cells to apoptosis and to investigate the relevance of E6-enhanced apoptosis to its other biological activities, we analyzed a BPV-1 E6 mutant (491, with four amino acids deleted at the C-terminus) for its ability to sensitize C127 cells to apoptosis. The result was then compared with the E6 mutant's ability to transform cells, to activate transcription, and to associate with known cellular binding proteins. Our data indicated that the transcriptional activation function of BPV-1 E6 correlated with sensitization of cells to TNF-mediated apoptosis. Moreover, functions required for BPV-1 E6-mediated sensitization of cells to apoptosis are distinct from those required for transformation. A potential role of paxillin in E6 sensitization of cells to apoptosis is implicated. These results thus indicate that sensitization of cells to TNF-induced apoptosis represents a novel function of BPV-1 E6.